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Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.
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Objective:To explore the efficacy and safety of domestic RECO flow restoration device in acute intracranial large-vessel occlusion (LVO).Methods:This study was a multicenter, prospective, randomized, open, controlled trial; 136 patients with acute intracranial LVO at 7 Chinese stroke centers from February 2014 to August 2016 were randomly assigned into an experimental group (thrombectomy by RECO device, n=67) and a control group (thrombectomy by Solitaire device, n=69). The efficacy and safety of patients from the two groups were compared and analyzed. The primary efficacy end point was set as achievement of good recanalization (modified thrombolysis in cerebral infarction [mTICI] grading≥2); the secondary efficacy end points included good prognosis (modified Rankin scale scores≤2 90 d after thrombectomy), time from puncture to achieving good recanalization/time from puncture to final angiogram on condition that good recanalization was not gained, or mortality within 90 d of thrombectomy. The safety end points included any device-related serious adverse events, symptomatic intracerebral hemorrhage or serious adverse events within 24 of thrombectomy. Results:There was no statistically significant difference between the experimental group and the control group in successful rate of good recanalization (91.0% vs. 86.9%), good prognosis rate (62.7% vs. 46.4%), time from puncture to achieving good recanalization/time from puncture to final angiogram on condition that good recanalization was not gained([85.4±47.0] min vs. [89.9±53.3] min), and mortality within 90 d of thrombectomy (13.4% vs. 23.2%, P>0.05). There were no device-related serious adverse events in all patients. No significant differences were found in the incidences of symptomatic intracranial hemorrhage (1.5% vs. 7.4%) or serious adverse events (death [1.5% vs. 1.4%] and brain hernia [4.5% vs. 0.0%]) between the two groups ( P>0.05). Conclusion:The domestic RECO flow restoration device is an effective and safe mechanical thrombectomy stent retriver for acute intracranial LVO.
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Two male patients aged 33 and 38 years with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)admitted in our hospital in 2016 and 2017 were reported.The main symptoms included abdominal pain and distension,numbness and weakness of the limbs.MRI showed mild ventriculomegaly with deepened sulcus and widened cerebral fissure,deepened bilateral cerebellar sulcus and the widened cleavage,atrophy of cerebellum and brainstem,and manifestations of acute cerebral infarction.Gene analysis showed mutation of mitochondrial DNA(mtDNA) A3243G.After definite diagnosis was made,patients reveived coenzyme Q10,ATP and vitamin supplements for improving circulation,and neurotrophic drugs for symptomatic treatment.The symptoms were slightly improved after treatment and two cases were followed-up as outpatients.
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Objective@#To analyze the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) and risk factors for central lymph node metastasis(CLNM) in PTMC.@*Methods@#The data of 900 patients with PTMC initially treated in our hospital from January 2004 to December 2015 were retrospectively analyzed. Chi-square test and Logistic regression analysis were performed to determine the risk factors for CLNM.@*Results@#CLNM affected 162 (22.9%) of 707 patients treated with central lymph node dissection. Age, maximum tumor size, multifocality, bilaterality, and extracapsular spread (ECS) were significantly correlated with CLNM (all P<0.01). Age<45 years, maximum tumor size>5 mm, multifocality, bilaterality, and extracapsular spread were independently correlated with CLNM.@*Conclusion@#A prophylactic central lymph node dissection should be considered in PTMC patients with age<45 years, maximum tumor size>5 mm, multifocality, bilaterality, and extracapsular spread.
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Objective To observe the inhibited effect of gastrodin on chemotherapy-induced neuropathic pain and its mechanism.Methods Fifty SD rats,chosen according to the threshold of pain,were randomly divided into 5 groups(n=10):control group,model group,and gastrodin treatment groups (30 mg/kg,60 mg/kg and 120 mg/kg).Vincristine (125 μg/kg,i.p.) was administered on alternate days to establish chemotherapy-induced neuropathic pain models in the model group and gastrodin treatment groups,and then,on the 9th d of modeling rats in the gastrodin treatment groups were treated with different doses of gastrodin,while those in the control group and model group were given normal saline on the 16th d of modeling.Paw withdrawal mechanical threshold and thermal pain threshold were measured;protein expressions of CX3CR1 and p-p38MAPK were detected by Western blotting,and tumor necrosis factor α (TNF-α) protein expression was detected by ELISA.Results As compared with control group,model group had significantly decreased pain threshold and increased protein expressions of CX3CR1,p-p38MAPK and TNF-α (P<0.05);as compared with those in the model group,the pain threshold increased and the expressions of CX3CR1,p-p38MAPK and TNF-α decreased in 60 mg/kg and 120 mg/kg gastrodin treatment groups,with significant differences (P<0.05).Conclusion Gastrodin can relieve the chemotherapy-induced neuropathic pain,probably by inhibiting the expressions of CX3CR1 and p-p38MAPK in the activation passageway of microglial cells in the spinal cord,and then,reducing the expression of TNF-α.
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[ABSTRACT]OBJECTIVETo explore the occurrence and development of nasal polyps by studying the interleukin 17 and vascular endothelial growth factor expression level in nasal polyp tissues.METHODSNasal polyps in 30 patients with chronic sinusitis (with polyps), ethmoid sinus mucosa in 30 patients with chronic sinusitis (without polyps), inferior turbinate mucosa in 10 patients with nasal septum deviation were collected intraoperatively. IL-17 and VEGF expression were detected using immunohistochemistry SP testing, and correlation between them was analysed. RESULTS1. The expression of IL-17 and VEGF in nasal polyps group is significantly higher than that of the other two groups.There was significant difference between each two groups statistically (P<0.01). 2. The expression of IL-17 was positively correlated with VEGF expression in nasal polyps.CONCLUSION1. The expression of IL-17 and VEGF increased in nasal polyp tissues. 2. The expression of IL-17 and VEGFwas positively correlated in nasal polyps , and both of them take part in the occurrence and development of nasal polyps.
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γ-Secretase is aⅠtransmembrane protease associated with Alzheimer disease(AD), and including four subunits:presenilin,presenilin enhancer-2,anterior-pharynx-defective1 and nicastrin. In recent studies,the ultra-high-resolution cryo-electron microscope has been used for the first time, revealing the humanγ-secretase″horseshoe″,the three-dimensional structure and the arrangement of the subunits. This technique has shed light on the regulation of the enzyme pathway and mechanism. In addition,the γ-secretase modulators,including non-steroidal anti-inflammatory drugs,have been shown in vitro to inhibit γ-secretase activity and selectively reduce the level of Aβ42 against AD. They have provided an effective approach,with broad prospects for development. Studies in this area have become a hot topic in recent years. Here we summarized the γ-secretase subunits regulatory pathways, humanγ-secretase fine three-dimensional structure andγ-secretase modulators .
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Objective To explore significance of Ligustrazine on acute cerebral infarction rat model and its effects on hydrogen sulfide, plasma bilirubin and oxidized low density lipoprotein level.Methods 100 healthy SD rats, ( 250 ±30 ) g, male or female, were divided into five groups ( control group, sham operation group, model group, western medicine group, and Ligustrazine group) ,each had 20.Experimental groups prepared focal cerebral ischemia model with suture method.Normal group, model group and the sham group once daily intravenous injected sterile saline 10 mL, Ligustrazine intravenous injection group injected Ligustrazine 10 mL/(kg? d), the WM group intravenous injected atorvastatin 10 mL/(kg? d).Half of the rats were sacrificed at 10 days of the experiment to detect the relevant indicators, at 20 days, the remaining rats in each group were sacrificed.Blood hydrogen sulfide, plasma bilirubin and oxidized LDL levels were detected, and brain pathology change were observed.Results Compared with control group and sham group, in Ligustrazine group and western medicine group,hydrogen sulfide and plasma bilirubin levels increased significantly, and the difference was statistically significant (P<0.05);after 20 days of treatment, compared with western medicine group Ligustrazine group hydrogen sulfide and plasma bilirubin levels rose more significant (P<0.05).Compared with control group and sham group, in Ligustrazine group and western medicine group, OxLDL levels decreased significantly, the difference was statistically significant (P<0.05); after 20 days of treatment, compared with western medicine group, OxLDL levels in Ligustrazine group decreased more significant ( P<0.05 ) .The rats brain histopathology examination showed that, Ligustrazine group:few nerve cell death, cytoplasm loose and swelling reduced significantly;WM group:condensation nuclei rare, brain edema relieve;model rats: brain tissue surrounding the nerve yuan swelling and the emergence of shrinkage, nuclear condensation within the infarct cells and vascular necrosis of normal tissue disappeared, fuzzy structure, interstitial edema; the control group and the sham-operated rats: normal cell morphology, distribution, no cortical Ministry pale infarction.Conclusion Ligustrazine can increase acute hydrogen sulfide, plasma bilirubin levels in rats with cerebral infarction, elevate level of oxidized low-density lipoprotein, has clinical significance.
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Objective To study and analyze the long-term video electroencephalography (VEEG) and clinical characteristics of children with Rolandic discharge.Methods Twenty-seven children with Rolandic discharge,admitted to our hospital from October 2009 to June 2013,were chosen in our study; theit clinical characteristics,VEEG results,imaging results,treatments and prognosis were retrospectively analyzed.Results In these 27 patients,19 had benign epilepsy with centrotemporal spikes (BECT),low-dose antiepileptic drug oxcarbazepine could obtain good efficacy in 15 patients and the other 4 did not give drug because of few seizures,and generally the prognosis was good; 2 had variants of BECT (therapy of antiepileptic drugs and corticosteroids had efficacy); 3 had symptomatic epilepsy (one was infantile autism,the other was encephalitis sequela,the last one was focal cortical dysplasia; therapy of antiepileptic drugs was combined,the result of the first one was good,the second one was not good,and the third was cured by surgery); and one had benign childhood occipital epilepsy and two had Tourette's syndrome.The VEEG of all 27 children showed numerous or single spikes on one side or both sides in Rolandic areas during wake-up and sleep; a few of them presented electrical status epilepticus during slow wave sleep.Conclusions Rolandic discharges in children are mostly seen in BECT,and secondly in symptomatic epilepsy and the variants of BECT,and sometimes in childhood occipital epilepsy and non-epilepsy children.VEEG monitoring can help the diagnosis and estimate the prognosis and instruct the therapy.
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Objective To study the effect and safety of intra-arterial thrombolysis combined with mechanical ad-juvant in the treatment of acute large artery occlusive infarction of anterior circulation and posterior circulation. Methods Fourty-tow patients were divided into anterior circulation group (24 cases) and posterior circulation group(18 cases). The recanalization rate, NIHSS score (National Institute of Health stroke scale), GCS score ( Glasgow coma score,GCS), BI ( Barthel Index) excellent rate, symptomatic intracranial hemorrhage rate and mortality was analyzed after intra-arterial thrombolysis combined with mechanical aids therapy. Results The anterior circulation group was mainly caused by car-diogenic embolism (15/24, 62.5%) and posterior circulation group was mainly caused by atherosclerosis thrombosis (5/18, 72.2%). The NIHSS score was significantly lower after treatment (8.3±4.9 vs. 8.1±5.7) than before treatment(15.1±5.3 vs. 16.8±7.8)(P=0.001 vs. P=0.001), the GCS score was significantly higher after treatment(13.9±4.4 vs. 12.8±4.2)than be-fore treatment(9.5 ± 3.8 vs. 9.6 ± 3.7)(P=0.001 vs. P=0.021). The symptomatic intracranial hemorrhage rate was signifi-cant higher in anterior circulation group (5/24, 20.8%) than in posterior circulation group (0,0%) (P<0.05). Compared with the anterior circulation group, the recanalization rate trended to increase in posterior circulation group (P=0.830).The symptomatic intracranial hemorrhage rate in anterior circulation group (5/24,20.8%) was significant higher than in pos-terior circulation group (0,0%) (P<0.05), the mortality was similar between these two groups. Conclusions Intra-arterial thrombolysis combined with mechanical adjuvant therapy can improve neurological deficit in acute large artery occlusive infarction and increase the recanalization rate,which is more suitable for the treatment of posterior circulation infarction.
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Objective To evaluate the effect and safety of intravenous (IV) thrombolysis, intra-arterial (IA) thrombolysis and mechanical adjuvant intra- arterial thrombolysis (IA + MA) in treating cardiogenic cerebral embolism. Methods A total of 66 patients with cardiogenic cerebral embolism were randomly divided into IV group (n = 25), IA group (n = 18), IA + MA group (n = 23). The artery recanalization rate, NIHSS score, GCS score, BI excellent rate, symptomatic intracranial hemorrhage rate and mortality after different thrombolytic therapies were determined. The results were compared between each other among the three groups. Results In all three groups both the post-treatment NIHSS score and GCS score were significantly improved when compared with pre-treatment ones (P < 0.05). In IA + MA group the artery recanalization rate was 78.3%(18/23) and the BI excellent rate was 40%(10/25), which were significantly higher than those in IV group (P < 0.05). The symptomatic intracranial hemorrhage rate in IA group was 5.6%(1/18), which was strikingly lower than that in IV group (32%, 8/25). Analysis of the causes showed that the artery recanalization rate in patients with valvular heart disease or cardiac myxoma was rather lower, but the intracranial hemorrhage rate and mortality in these patients were much higher. Conclusion Thrombolytic therapy can improve neurological deficit in cardiogenic cerebral embolism, and the therapeutic effect of mechanical adjuvant intra- arterial thrombolysis is definitely better.
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Objective To investigate the role of soluble cytotoxic T-lymphocyte associated antigen-4 (sCTLA-4) in the pathogenesis of myasthenia gravis (MG) in Fujian province.Methods A total of 80 patients with MG and 80 sex-and age-matched healthy controls were enrolled in the study .MG patients were divided into non-glucocorticoid treatment group and glucocorticoid treatment group , and the latter was further divided into immunosuppressive therapy group and thymusectomy group .Concentrations of sCTLA-4 in ser-ums from above mentioned groups were measured by enzyme-linked immunosorbent assay (ELISA).Results The concentrations of sCTLA-4 in both non-glucocorticoid treatment group and glucocorticoid treatment group were significantly higher than those in the healthy control group (6.03 ng/ml±3.58 ng/ml, 3.44 ng/ml± 2.36 ng/ml vs.0.49 ng/ml±0.95 ng/ml) (χ2=100.67, P<0.001), but sCTLA-4 concentrations in glu-cocorticoid treatment group were lower than those in non-glucocorticoid treatment group (Z=-3.37,P=0.001).With the treatment of glucocorticoid, the sCTLA-4 concentrations were reduced (6.03 ng/ml± 3.58 ng/ml vs.4.56 ng/ml±2.08 ng/ml;t=3.10, P=0.005), and the concentrations of sCTLA-4 were also decreased after thymusectomy therapy (3.86 ng/ml±2.53 ng/ml vs.2.59 ng/ml±2.37 ng/ml; Z=-2.21, P=0.04).However, there was no significant difference in the concentrations of sCTLA-4 before and after immunosuppressive drugs treatment (Z=-1.26,P=0.21).Conclusion The concentration of sCTLA-4 was increased in patients with MG , but with the treatment of glucocorticoid or thymusectomy it could be reduced .
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Objective To research into the current situation of basic medicine knowledge grasp of non-medical students in local comprehensive university and to discuss the significance and necessity of launching basic medicine knowledge education in comprehensive university.Methods Random sampling was used to survey non-medical students of 1-3 grades in three gorges university with questionnaire.SPSS 13.0 software was used to do statistical analysis.Results 89.1% undergraduates had consciousness to deal with slight illness and slight wound by themselves and 95.4% undergraduates would prepare some drug to use when necessary.But only 37.2% undergraduates knew the medicine classification management method of our country and 94.2% undergraduates might abuse common medicine.96.7% undergraduates thought that popularizing basic medicine knowledge by selected courses in university was necessary.Conclusions Most undergraduates lack basic medicine knowledge and potential medicine safety hazard like abuse medicine is existed.Education on basic medicine knowledge in university is of great significance in improving the life quality and basic quality of undergraduates.
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Eight cases of hypothyroid myopthy admitted in Zhanshan Hospital Xiamen University from 1995 to 2011 were retrospectivrely analyzed.The main clinical features were proximal muscle weakness,susceptibility to fatigue,and elevation of muscle enzymes.Electromyography revealed no specific findings.All patients obtained clinical recovery after thyoid hormone replacement.Hypothyroid myopathy should be considered in cases of muscle weakness and elevation of muscle enzymes.
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Objective To explore the diagnosis and treatment of cerebral embolism from pulmonary embolism (PE).Methods The clinical data of 5 cases with PE accompanied by cerebral embolism covering a period from October of 2007 to July of 2011 were retrospectively analyzed.Results In this study,the average age of 5 cases (all female) was 46.5 years old.PE was diagnosed through enhanced CT and ECT in lung among all 5 cases.Moderate to severe pulmonary hypertension was confirmed by echocardiogram.Two cases was patent foramen ovale and one was congenital atrial septal defect.Each patient was diagnosed to be new-onset cerebral infarction by MRI.Three cases underwent cerebral arterial thrombolysis.All of them survived and long-term anticoagulant treatment with Warfarin.INR was adjusted between 2.0 and 2.5 by change of Warfarin dose.Among them,one patient had cerebral embolism again just 3 days after the latest cerebral embolism; the other 4 patients did not suffer from cerebral embolism during the follow-up.Conclusions Paradoxical cerebral embolism is common.For clinical patients with PE,especially pulmonary hypertension accompanied by systemic circulation arterial embolism or unexplained systemic cerebral arterial embolism,paradoxical cerebral embolism should be considered.
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Two isolation methods for sorting of endothelial progenitor cells (EPCs): from peripheral blood mononuclear cells (PBMCs) and CD133(+) enriched cells were compared, by defining the cell morphology, phenotype, reproductive activities and function in vitro, to provide a reference for clinical application of EPCs. PBMCs from healthy subjects were used either directly for cell culture or for CD133(+) sorting. The two groups of cells were cultured in complete medium 199 (M199) for 7 to 14 days and the phenotypes of EPCs were analyzed by FACS. The proliferation of differentiated EPCs was studied by MTT assay, and the VEGF concentration was measured using an ELISA kit. ECM gel experiment and migration assay were performed in vivo. The results showed that PBMCs produced more colony-forming units (CFU) than CD133(+) enriched cells from the same volume of blood (P<0.01). From day 7 to 14, the two groups showed decreased expression of hematopoietic stem cell markers and increased level of endothelial markers, but CD144(+) cells in CD133(+) group were less than in PBMCs group (P<0.01). PBMCs group secreted more VEGF than CD133(+) group on the day 7 (P<0.01). As compared with CD133(+) group, PBMCs group had more potent potential of proliferation and vascularization in vitro. It was concluded that CD133(+) sorted cells showed a lower capacity of differentiation, secretion, proliferation and vascularization in vitro, suggesting that CD133-negative cells may be a preferential way to get EPCs for clinical therapy.
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AIM: To compare the methods of two currently employed isolation methods for endothelial progenitor cells (EPCs): from total peripheral blood mononuclear cells (PBMCs) and from enriched CD133~+ cells, by defining the cell morphology, phenotype, reproductive activities and function in vitro, providing a reference for clinic application. METHODS: PBMCs from the healthy subjects were used for CD133~+ sorting or not. The two groups of isolated cells were suspended in complete medium M199 for 7 d to 14 d. EPCs phenotype were characterized by FACS. The proliferation of differentiated EPCs was studied by MTT assay, and VEGF concentration was measured using an ELISA kit. Matrigel experiment and migration assay were imitated vascularization in vivo. RESULTS: PBMCs produced more colony-forming units (CFU) than CD133~+ cells from the same volume of blood (P<0.01). From 7 d to 14 d, the two groups show decreased expression of hematopoietic stem cell markers and increased level of endothelial markers, but CD144~+ cells in CD133~+ group were lower than those in PBMCs groups (P<0.01). Cells in PBMCs group secreted more VEGF than that in CD133~+ group on 7 d (P<0.01). Compared to CD133~+ group, PBMCs group showed more potential of proliferation and vascularization in vitro. CONCLUSION: CD133~+ sorted cells show a lower capacity of differentiation, secretion, proliferation and vascularization in vitro, which is unable to differentiate to mature endothelial cells, indicating that it's not a preferential way to obtain EPCs for clinic therapy.
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Objective To evaluate the efficacy of zoledronic acid combined with radiotherapy for metastatic bone tumours. Methods Eighty patients with metastatic bone tumour by meta were randomly derided into two groups study group(n=40), and the eantrol group (n=40). The study group received 4 mg zoledronic acid infusion for 15 minutes combined with radiotherapy (DT 30Gy/10f/2w) ,control group was only treated with radiotherapy. The primary effective parameters were pain scores, quality of life, KPS scores and pain relief rates. The vital signs, bi-ochemical and hematological parameters were determined. Results The overall response rates of study group and control group were 97.5% and 72.5% ,respectively(P<0.05). The overall response rate of movement capacity im-provement was 87.5 % in the study group and 65.0% in the control group(P<0.05). There was statistical signifi-cance of QOL and KPS in two groups (P<0.01). An adverse event of mild systemic skeletal pain was recorded after pamidronate infusion and completely reversed after 8 hours. Conclusion Zoledronic acid combined with radiothera-py is effective and safe for treating malignant tumour with mestastatic bone tumours. It is a better way to treat meta-static bone tumors at present.
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[Objective] To mensurate and compare with the mensuration of alkaloid and saponin in the flower,pedicel and bulb of fritillariae thuubergii,make full use of all parts of fritillariae thuubergi.i[Method]To mensurate the mensuration of alkaloid and saponin in the three parts of fritillariae with the twophase titration method and gravimetric method.[Result]The mensuration of alkaloid in the flowers of fritillariae thuubergii is 0.182%,while it is 0.047% and 0.341% in the pedicel and bulb separately,and the mensuration of saponin in the flowers of fritillariae thuubergii is 5.112%,while it is 8.840% and 1.724% in the pedicel and bulb separately.[Conclution] The difference of major component in the fritillariae thuubergii offers the foundation to make full use of the flowers,pedicel and bulb.
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This article discusses the important effect of language techniques in the pharmacology teaching,according to the peculiarity of this speciality and the experience of author,and the concrete language techniques to activate the class to attract the students' attention and to improve teaching effect from the aspects of the basic request of language expression in class,the scientificity and the logicality and the enlighten and techniques of teaching language in pharmacology class.It also explains the importance of language techniques in the pharmacology teaching from many aspects.